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Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer

 Nicholas C Turner  ;  Mafalda Oliveira  ;  Sacha J Howell  ;  Florence Dalenc  ;  Javier Cortes  ;  Henry L Gomez Moreno  ;  Xichun Hu  ;  Komal Jhaveri  ;  Petr Krivorotko  ;  Sibylle Loibl  ;  Serafin Morales Murillo  ;  Meena Okera  ;  Yeon Hee Park  ;  Joohyuk Sohn  ;  Masakazu Toi  ;  Eriko Tokunaga  ;  Samih Yousef  ;  Lyudmila Zhukova  ;  Elza C de Bruin  ;  Lynda Grinsted  ;  Gaia Schiavon  ;  Andrew Foxley  ;  Hope S Rugo  ;  CAPItello-291 Study Group 
 NEW ENGLAND JOURNAL OF MEDICINE, Vol.388(22) : 2058-2070, 2023-06 
Journal Title
Issue Date
Antineoplastic Combined Chemotherapy Protocols / adverse effects ; Antineoplastic Combined Chemotherapy Protocols / therapeutic use ; Aromatase Inhibitors* / adverse effects ; Aromatase Inhibitors* / therapeutic use ; Breast Neoplasms* / drug therapy ; Breast Neoplasms* / pathology ; Double-Blind Method ; Female ; Fulvestrant / adverse effects ; Fulvestrant / therapeutic use ; Humans ; Male ; Neoplasm Recurrence, Local / drug therapy ; Proto-Oncogene Proteins c-akt ; Receptor, ErbB-2
BACKGROUND: AKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited. METHODS: In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed. RESULTS: Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo. CONCLUSIONS: Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.). Copyright © 2023 Massachusetts Medical Society.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
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